Protective Effect of TA-993, a Novel Therapeutic Agent for Peripheral Circulatory Insufficiency, on Skeletal Muscle Fatigue in a Rat Model of Hindlimb Ischemia

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Abstract

TA−993(cis−(−)−2−(4−methylphenyl)−3−acetoxy−2, 3−dihydro−5−(2−dimethylaminoethyl)−8−methyl−1, 5−benzothiazepine−4(5H)−one maleate), a new 1, 5−benzothiazepine derivative, has a selective increasing action on limb blood flow in addition to an antiplatelet action.In this report we studied the effect of TA−993 on a time dependent decrease in developed tension of electrically−induced contraction of tibialis anterior muscle in a rat model of peripheral circulatory insufficiency induced by occlusion of abdominal aorta.In our preparation, the developed tension decreased by 20−30% in a sham−operated group and 30−40% in an abdominal aorta−occluded group at the end of the experimental period of 60 min.Intraduodenal administration(i.d.)of TA−993(10 mg/kg)to the abdominal aorta−occluded rats ameliorated the decrease in developed tension to the level of the sham−operated group.Moreover, TA−993 at 10 mg/kg, i.d.significantly increased femoral arterial blood flow supplied through collateral circulation and decreased the whole blood viscosity in this model.These results suggest that TA−993 improves dysfunction of skeletal muscle contraction due to peripheral circulating insufficiency through an increase in collateral blood flow and an improvement of red blood cell deformability.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 83(1), 73-81, 2000-05-01

    The Japanese Pharmacological Society

References:  19

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008184451
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5399726
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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